Bilirubin induces loss of membrane lipids and exposure of phosphatidylserine in human erythrocytes
Bilirubin induces loss of membrane lipids and exposure of phosphatidylserine in human erythrocytes
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DOI：
10.1023/a:1015563704551
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发表时间：
2002-01-01
影响因子：
6.1
通讯作者：
Brites, D
中科院分区：
文献类型：
--
作者：
Brito, MA;Silva, RFM;Brites, D
当胆红素与白蛋白的摩尔比超过1时，未结合的胆红素会越来越多地与红细胞结合，导致中毒表现，最终导致细胞溶解。我们以前的研究表明，胆红素可以诱导红细胞膜的脂质释放。在目前的工作中，这些研究被扩展，以表征膜脂成分的变化，并评估胆红素是否导致磷脂不对称性的丧失。为此，将人的红细胞与几种胆红素与白蛋白的摩尔比(0.5至5)孵育，并测定胆固醇以及总磷脂和个别磷脂的种类。为了检测外表面有磷脂酰丝氨酸的红细胞，将其与白蛋白的摩尔比固定为3，与胆红素孵育后，测定膜联蛋白V阳性细胞的数量。结果表明，红细胞膜的组成发生了深刻的变化，包括修饰的胆固醇和磷脂含量。膜胆固醇的释放，以及总磷脂和个别磷脂在摩尔比大于或等于1的情况下的释放，表明重症黄褐斑新生儿可能会发生红细胞损伤。内位磷脂、磷脂酰乙醇胺和磷脂酰丝氨酸的丢失，表明磷脂在膜双层中重新分布。细胞外表面磷脂酰丝氨酸的暴露证实了这一点。综上所述，本研究证实胆红素可导致人红细胞膜脂质的丢失和磷脂酰丝氨酸的外化。这些特征可能促进溶血和红细胞吞噬，从而在严重的新生儿高胆红素血症时导致胆红素生成增加和贫血。
Unconjugated bilirubin increasingly binds to erythrocytes as the bilirubin-to-albumin molar ratio exceeds unity, leading to toxic manifestations that can culminate in cell lysis. Our previous studies showed that bilirubin induces the release of lipids from erythrocyte membranes. In the present work, those studies were extended in order to characterize the alterations of membrane lipid composition and evaluate whether bilirubin leads to a loss of phospholipid asymmetry. To this end, human erythrocytes were incubated with several bilirubin-to-albumin molar ratios (0.5 to 5), and cholesterol as well as the total and the individual classes of phospholipids were determined. To detect erythrocytes with phosphatidylserine at the outer surface, the number of annexin V-positive cells was determined following incubation with bilirubin, fixing its molar ratio to albumin at 3. The results demonstrate profound changes in erythrocyte membrane composition, including modified cholesterol and phospholipid content. The release of membrane cholesterol, as well as of total and individual classes of phospholipids at molar ratios greater than or equal to1, indicates that damage of erythrocytes may occur in severely ill jaundiced neonates. The loss of the inner-located phospholipids, phosphatidylethanolamine and phosphatidylserine, points to a redistribution of phospholipids in the membrane bilayer. This was confirmed by the exposure of phosphatidylserine at the outer cell surface. In conclusion, this study demonstrates that bilirubin induces loss of membrane lipids and externalization of phosphatidylserine in human erythrocytes. These features may facilitate hemolysis and erythrophagocytosis, thus contributing to enhanced bilirubin production and anemia during severe neonatal hyperbilirubinemia.